Tuberculosis is the leading cause of death due to infectious and it has been estimated that 1/5th of global population is infected and at least 3 million people succumb to the disease. It is known to relapse among the elderly and the debilitated. Immuno senescence has been generally held to be responsible for enhanced susceptibility and investigators have used the mouse animal model to dissect the underlying mechanism. Previous studies using C57B1/6 mice have however yielded paradoxical results: both young and old C57B1/6 mice showed apparently normal macrophage function, T-cell receptor repertoire and application of memory responses following infection with MTB. However, unlike the younger generation, the older mice showed 'defects' in the expression of surface adhesions/intergrins on T-cells which normally enable homing and infiltration of T cells into lungs for effective control of lung tuberculosis. Dysregulation of adhesions/intergrins thus appears to play a pivotal role in immunosenesdence and susceptibility, although the molecular mechanisms leading to the dysregulation remain enigmatic. We developed mouse models to illustrate acute, chronic and reactivation of tuberculosis using A/J and C57B1/6 mice. The A/J mice were found strictly more susceptible to tuberculosis and reactivated with TB faster compared to C57B1/6 mice. Increased susceptibility of A/J mice was associated with C5 deficiency as confirmed by using C5 knockout mice. Interestingly, C5 deficiency was also associated with a poor granuloma formation in the lungs following MTB infection and the disease occurred in mice, which were relatively young. These data together with the observation that C5 derived C5a can regulate the expression of adhesions/intergrins molecules suggested that immune responses are defective in A/J. Indeed, dysregulation of adhesions/intergrins in A/J may present as an accelerated aging phenomenon leading to enhanced susceptibility to intracellular pathogens. This investigation will therefore examine the hypothesis that C5 deficiency causes reduced expression of adhesions/intergrins molecules on T cells interfering with the structure and function of granuloma formation and ultimately with control of TB. Splenetic lymphocytes from mice under varying stages of reactivation tuberculosis will be immunophenotyped using flow cyctometry for distinct adhesions/intergrins molecules (e.g., ICAM-1, p selectin) that may suggest defects in infiltration and homing patterens.